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Drug-Resistant TB Should Figure Prominently In The Global AMR Response

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On 21 September 2016, the President of the UN General Assembly will convene a one-day high-level meeting at the UN Headquarters in New York on "Antimicrobial Resistance" (AMR) with the participation of Member States, NGOs, civil society, the private sector and academic institutions.

This is timely and welcome, because AMR is a major health threat, and it is estimated that by 2050, 10 million lives a year and a cumulative 100 trillion USD of economic output are at risk due to the rise of drug-resistant infections.

Everyone should watch this incredible video by Harvard and Technion-Israel Institute of Technology researchers who set up a giant petri dish to see how microbes evolve even when antibiotics are present in the dish at increasing powerful concentrations. The results are scary and show how mutations and natural selection can produce superbugs.

The objective of the UN meeting this week is to raise awareness about AMR, and secure strong national, regional and international political commitment in addressing AMR comprehensively and multi-sectorally. As a tuberculosis researcher, I am hoping that drug-resistant TB will figure prominently in the UN meeting as well as the international response to AMR.

Drug-resistant tuberculosis (DR-TB) is a perfect example of the threat posed by AMR. The most common form drug-resistant TB is multi-drug resistant TB (MDR-TB), which means that TB bacteria are resistant to two of the best first-line antibiotics -- isoniazid and rifampicin.

Drug-resistant TB is a nightmare for patients and doctors.

Globally in 2014, WHO estimated 3.3 per cent of new cases and 20 per cent of previously treated cases to have MDR-TB. Studies show that an estimated 480 000 people developed MDR-TB in 2014 and 190 000 people died. Even children are impacted by DR-TB, with recent estimates suggesting that MDR-TB in children may be far more prevalent than previously understood.

Extensively drug-resistant (XDR-TB) strains are resistant to at least four of the core anti-TB drugs, and XDR-TB has been reported by 105 countries in 2014. About 10 per cent of people with MDR-TB have XDR-TB. Some studies have also reported totally drug-resistant strains of TB, resistant to all antibiotics tested. This is a TB 'superbug' that is virtually untreatable and takes us back to the sanatorium era, where we had very little to offer patients with TB, except for bed rest and sun light.

Drug-resistant TB is a nightmare for patients and doctors. Patients have to endure a prolonged (up to two years) and toxic treatment with multiple drugs, including painful injections. Stories of people who have battled and survived TB show the devastating impact of DR-TB. One in two patients with drug-resistant TB die because of it. Treatment of DR-TB is also very expensive because of the high cost of second-line TB drugs.

It is much smarter and cheaper to prevent DR-TB than treat it. And prevention of DR-TB requires better access to drug-resistance testing, high-quality treatment, access to new TB drugs, infection control, and increased political commitment with financing.

Unfortunately, high TB burden countries are yet to seriously address these priority actions to tackle DR-TB. In many countries, only a quarter of MDR-TB patients are detected, and not even half of all patients with DR-TB are on second-line drug therapy. Quality of TB care for even drug-susceptible TB remains suboptimal in many countries, especially in countries with large numbers of private health care providers. In such settings, doctors prescribe irrational drug regimens, and adherence monitoring is poor.

Empirical antibiotic use is widespread in many countries with weak regulation, and healthcare providers tend to use antibiotics as diagnostic tools; this further increases the risk of AMR. Also, over-the-counter (OTC) antibiotic abuse is widespread in many high TB burden countries, as we recently showed in a study in India, using mystery patients. OTC use of fluoroquinolones, a widely used antibiotic, can delay the diagnosis of TB, and also increase the risk of DR-TB. This is particularly relevant, since some of the emerging new TB drug regimens contain fluoroquinolones (i.e. Moxifloxacin).

While highly accurate and rapid molecular tests such as Xpert MTB/RIF are now available to quickly detect TB as well as drug-resistance, most high-burden countries are still reliant on sputum smear microscopy, a technology that is not only insensitive but also incapable of detecting drug-resistance. This means patients are often managed with no information on drug-susceptibility test results. This approach of treating TB 'blindly' is no longer tenable in places such as Mumbai, where DR-TB is a widespread problem.

A recent report called 'Out of Step" by MSF and Stop TB Partnership found major gaps in how TB tools and policies are implemented. For example, only eight of 24 countries included in the survey had revised their national policies to include Xpert MTB/RIF as the initial diagnostic test for all adults and children with presumptive TB, replacing smear microscopy. Six of 24 countries, including India, still recommended intermittent treatment for drug-sensitive TB (which is less effective than daily therapy).

Even simple interventions such as fixed dose combination pills to improve treatment adherence are not routinely used in all countries. Although new TB drugs (e.g. bedaquiline and delamanid) are now available, many countries are yet to make them available for patients who are running out of options. Such implementation failures are most definitely generating DR-TB and have to be urgently addressed.

A major reason behind poor TB control is the fact that TB is a low priority for many developing countries, and current TB budgets are insufficient to make progress in addressing DR-TB. Most National TB Programs in high burden countries are seriously under-funded, and, sadly, even emerging economies such as India are not spending enough on TB.

In this context, it may be more impactful for DR-TB control to be seen as one component of a comprehensive strategy to address AMR. While TB gets little attention, AMR is increasingly seen as a global health emergency and a security threat. Policy makers and donor agencies have prioritized AMR as a key issue for the global health security agenda, and the upcoming UN meeting is one component of this global response.

As I have argued previously, the door is wide open for the TB community to leverage this interest, and advocate for a well-funded, comprehensive AMR initiative that includes DR-TB as a key component. In fact, DR-TB could well be a pathfinder for successfully tackling AMR in low and middle income countries, and help make the case for greater investments. It is time for the TB community to advocate for including TB in the broader agenda to tackle AMR globally, and make sure DR-TB receives adequate funding and support.

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