Editorial
In October, 2013, WHO released the Global Tuberculosis Report 2013 and its supplement Countdown to 2015, which provide a snapshot of the current global epidemic. Encouragingly, the report showed that the incidence of tuberculosis is declining by around 2% per year, and that several regions have met, or are on target to meet, the 2015 millennium development goal of a reduction in mortality of 50%, with a global reduction of 45% reported since 1990. However, this progress is hindered by the reality of drug-resistant tuberculosis and WHO has highlighted multidrug-resistant (MDR) strains as one of the key challenges that urgently needs to be addressed. Globally, 450 000 MDR cases were detected in 2012, with 170 000 deaths noted in the WHO report. MDR tuberculosis, where patients are resistant to isoniazid and rifampicin, was identified in 3·6% of newly diagnosed cases and in 20·2% of those previously treated for tuberculosis. Some patients also had extensively drugresistant (XDR) disease, where patients have additional resistance to a fluoroquinolone and a second-line injectable antibiotic; at least 92 countries reported at least one XDR case. So how have these cases arisen? Eastern Europe and central Asia had the highest levels of MDR cases, and countries such as China, Russia, and India with their vast geographies are a hotbed for the development of resistant cases. Recently reported drug stockouts in India and Russia will also result in more MDR cases. Indeed staff and drug shortages are a major driver of resistance. What can be done to reduce drug resistance was the focus of many discussions at the recent 44th Union World Conference on Lung Health held in Paris, France. Diagnostic testing with Xpert MTB/RIF has been rolled out in 77 countries in 2012, predominantly with donor support, and should help to tackle the missing tuberculosis cases by providing a simple point-of-care test. For example, less than 25% of those estimated to have MDR were detected in 2012. However, several experts agreed that the key concern was how to adequately treat patients. A number of questions were asked; such as which sequence of drugs should be recommended, how treatment regimens can be made easier for patients to complete, and how drugs can be made more palatable. One encouraging report at the meeting was on the pilot phase of a 9 month regimen for MDR cases, with a success rate of around 90% reported, and no failures or relapses. www.thelancet.com/respiratory Vol 1 December 2013
This regimen could help improve patient compliance by reducing treatment time from the usual 2 years to 9 months and these findings are important because new drugs or vaccines are rare in tuberculosis treatment. Last December, patients’ hopes were raised with the accelerated US FDA approval of bedaquiline on the basis of phase 2 evidence, although drug costs and difficulties in reaching patients in the community could limit this new drug’s effectiveness. How bedaquiline is rolled out must now be considered carefully to prevent resistance neutralising its effectiveness. Other forums at the meeting focused on children who have immune systems that are especially vulnerable to tuberculosis infection, and in endemic regions this coincides with risk factors such as tobacco smoke, poor living conditions, and infection with HIV, as well as exposure to family members with tuberculosis. Children might also become infected when accompanying adults to clinics. As a result, some practices have designed their buildings to ensure better ventilation and safe spaces for children, as well as separating clinic days for new patients not yet diagnosed with tuberculosis from those on treatment. Data for effective drug prophylaxis and drug pharmacokinetics are scarce in this group. Furthermore, drug formulations are often designed for adult consumption, and large pills can be difficult to swallow for small infants, and even more bitter when crushed, with consequent unknown efficacy and pharmacokinetics from the altered formulation. Issues surrounding consent and ethical dilemmas in completing research in this group add another layer of complexity to their care and protection. Finally, the current level of funding will hamper any efforts at MDR tuberculosis care and control. In 2011, US$0·6 billion were spent, whereas WHO estimates that $2 billion will be required to diagnose and treat MDR cases in 2015. Increasing domestic and international financing was one of five priority actions set out in the WHO report alongside addressing the MDR tuberculosis crisis, improving anti-retroviral coverage for patients with HIV, identifying missing cases of tuberculosis, and accelerating the rapid uptake of new tools. All of these factors will be vital in the fight against tuberculosis in the post-2015 UN agenda, but tackling resistance will need to be the focus if this scourge is to be beaten. ■ The Lancet Respiratory Medicine
David Mack/Science Photo Library
MDR tuberculosis challenges global health-care targets
See News page 762 For the WHO global report see http://www.who.int/tb/ publications/global_report/en/
755
In October, 2013, WHO released the Global Tuberculosis Report 2013 and its supplement Countdown to 2015, which provide a snapshot of the current global epidemic. Encouragingly, the report showed that the incidence of tuberculosis is declining by around 2% per year, and that several regions have met, or are on target to meet, the 2015 millennium development goal of a reduction in mortality of 50%, with a global reduction of 45% reported since 1990. However, this progress is hindered by the reality of drug-resistant tuberculosis and WHO has highlighted multidrug-resistant (MDR) strains as one of the key challenges that urgently needs to be addressed. Globally, 450 000 MDR cases were detected in 2012, with 170 000 deaths noted in the WHO report. MDR tuberculosis, where patients are resistant to isoniazid and rifampicin, was identified in 3·6% of newly diagnosed cases and in 20·2% of those previously treated for tuberculosis. Some patients also had extensively drugresistant (XDR) disease, where patients have additional resistance to a fluoroquinolone and a second-line injectable antibiotic; at least 92 countries reported at least one XDR case. So how have these cases arisen? Eastern Europe and central Asia had the highest levels of MDR cases, and countries such as China, Russia, and India with their vast geographies are a hotbed for the development of resistant cases. Recently reported drug stockouts in India and Russia will also result in more MDR cases. Indeed staff and drug shortages are a major driver of resistance. What can be done to reduce drug resistance was the focus of many discussions at the recent 44th Union World Conference on Lung Health held in Paris, France. Diagnostic testing with Xpert MTB/RIF has been rolled out in 77 countries in 2012, predominantly with donor support, and should help to tackle the missing tuberculosis cases by providing a simple point-of-care test. For example, less than 25% of those estimated to have MDR were detected in 2012. However, several experts agreed that the key concern was how to adequately treat patients. A number of questions were asked; such as which sequence of drugs should be recommended, how treatment regimens can be made easier for patients to complete, and how drugs can be made more palatable. One encouraging report at the meeting was on the pilot phase of a 9 month regimen for MDR cases, with a success rate of around 90% reported, and no failures or relapses. www.thelancet.com/respiratory Vol 1 December 2013
This regimen could help improve patient compliance by reducing treatment time from the usual 2 years to 9 months and these findings are important because new drugs or vaccines are rare in tuberculosis treatment. Last December, patients’ hopes were raised with the accelerated US FDA approval of bedaquiline on the basis of phase 2 evidence, although drug costs and difficulties in reaching patients in the community could limit this new drug’s effectiveness. How bedaquiline is rolled out must now be considered carefully to prevent resistance neutralising its effectiveness. Other forums at the meeting focused on children who have immune systems that are especially vulnerable to tuberculosis infection, and in endemic regions this coincides with risk factors such as tobacco smoke, poor living conditions, and infection with HIV, as well as exposure to family members with tuberculosis. Children might also become infected when accompanying adults to clinics. As a result, some practices have designed their buildings to ensure better ventilation and safe spaces for children, as well as separating clinic days for new patients not yet diagnosed with tuberculosis from those on treatment. Data for effective drug prophylaxis and drug pharmacokinetics are scarce in this group. Furthermore, drug formulations are often designed for adult consumption, and large pills can be difficult to swallow for small infants, and even more bitter when crushed, with consequent unknown efficacy and pharmacokinetics from the altered formulation. Issues surrounding consent and ethical dilemmas in completing research in this group add another layer of complexity to their care and protection. Finally, the current level of funding will hamper any efforts at MDR tuberculosis care and control. In 2011, US$0·6 billion were spent, whereas WHO estimates that $2 billion will be required to diagnose and treat MDR cases in 2015. Increasing domestic and international financing was one of five priority actions set out in the WHO report alongside addressing the MDR tuberculosis crisis, improving anti-retroviral coverage for patients with HIV, identifying missing cases of tuberculosis, and accelerating the rapid uptake of new tools. All of these factors will be vital in the fight against tuberculosis in the post-2015 UN agenda, but tackling resistance will need to be the focus if this scourge is to be beaten. ■ The Lancet Respiratory Medicine
David Mack/Science Photo Library
MDR tuberculosis challenges global health-care targets
See News page 762 For the WHO global report see http://www.who.int/tb/ publications/global_report/en/
755
