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Urgency Needed in the Global Response to Drug-resistant Tuberculosis

In the second of two linked posts, Lindsay McKenna and Colleen Daniels of Treatment Action Group (TAG) describe the importance of access to timely diagnosis and appropriate treatment for patients with drug-resistant tuberculosis and demand that urgency be returned to the global DR-TB response.

“Drs. Dalene and Arne von Delft” the second short film in the series Tuberculosis: Behind the Numbers commissioned by TAG and directed by Jonathan Smith, highlights a young, brave, South African doctor’s two-year battle with multidrug-resistant tuberculosis (MDR-TB), a form of tuberculosis (TB) resistant to two of the most powerful TB drugs, isoniazid and rifampicin.  Cure is only achieved in 50-60 percent of MDR-TB cases globally. Dr. Dalene von Delft’s diagnosis with MDR-TB was completely unexpected – she had what she believed to be a persistent dry cough and harmless sinusitis. Following MDR-TB diagnosis, Dalene underwent months of difficult treatment where she stomached 35 pills a day and endured painful daily injections. One of the injectable drugs in Dalene’s regimen was damaging her hearing and threatening to silence her world, a side effect that Dalene and her husband were unwilling to accept. They needed a replacement drug, but chronic under-investment in TB drug development left them to choose among a limited suite of decades-old drugs carrying high toxicities.

MDR-TB Behind the Numbers: Drs. Dalene and Arne von Delft from Visual Epidemiology on Vimeo.

Luckily Dalene obtained pre-approval access to bedaquiline, a novel drug recently approved by the U.S. Food and Drug Administration for MDR-TB, which saved both her hearing and her life. Dalene’s story underscores the need for more effective and less toxic TB drugs, and improved access to existing tools necessary to respond to the global drug-resistant TB (DR-TB) crisis, which has worsened since its recognition as an urgent threat to global health by the World Health Assembly in 2009.

Though DR-TB was around well before the 1990s when an outbreak in New York captured the world’s attention to these dangerous strains of TB, it was only at the 62nd World Health Assembly in May 2009, that health ministers from countries most affected by MDR-TB issued the Beijing Call for Action on Tuberculosis Control and Patient Care. Signatory countries to the Call for Action committed to scaling-up the diagnosis and treatment of multi and extensively drug-resistant TB (M/XDR-TB), a form of MDR-TB with resistance to floroquinolones and at least one of three second line injectable drugs, and to moving toward universal access to M/XDR-TB diagnosis and treatment by 2015. This resolution made clear that policy changes beyond the remit of national TB programs would be required to effectively fight DR-TB. The 2009 resolution gave hope for bold and radical policy change and renewed political will and investment in tackling DR-TB. However, this commitment to action has yet to materialize.

In the most recent Global Tuberculosis Report, the World Health Organization (WHO) estimated that there were 450,000 new MDR-TB cases. By 2013, 92 countries had reported at least one case of XDR-TB. Although alarming, we know that these estimates are flawed and likely underestimate the true extent of M/XDR-TB. After South Africa implemented Xpert MTB/RIF, a new diagnostic tool, the percentage of DR-TB cases among total TB cases diagnosed jumped from 1.8 percent to 5 percent. The increased number of DR-TB cases is likely not only a result of the spread of resistant strains, but also attributable to better and more widespread testing. Despite the increasing number of diagnosed DR-TB cases, country programs are still failing to respond to the global DR-TB emergency with the urgency required to get to universal TB diagnosis and treatment by 2015.

The first step in Dalene’s treatment was accurate diagnosis of MDR-TB, which allowed for initiation of treatment with an effective regimen. For the diagnosis of DR-TB, the WHO has recommended rapid drug susceptibility testing (DST) for isoniazid and rifampicin or for rifampicin alone above conventional methods or no testing at the time of TB diagnosis. Rapid diagnosis of TB and drug-resistance helps to expedite treatment initiation with drugs effective against the individual’s strain of TB. This is particularly important as delays in accurate diagnosis prevent patients from starting appropriate treatment, which leads to further transmission of infection and fosters drug-resistance. Line probe assays and other rapid molecular diagnostic tests like Xpert MTB/RIF have seen rapid scale-up in many countries, but limited infrastructure and laboratory capacity prevent universal, decentralized, rapid TB diagnosis and DST. As a result, millions of patients never receive any DST or the benefits of this life-saving technology.

While many countries have improved access to TB diagnosis and DST, there remains a wide chasm between WHO guidelines and national implementation. For example, four city districts in Lima, Peru (a country renowned for its advanced response to MDR-TB) each have a reference laboratory capable of performing first-line DST using culture techniques. Results using these methods can take anywhere from 2 weeks to 2 months to identify drug resistance, while first-line DST results using rapid molecular tests take just 2-5 hours. All first-line DST results are confirmed at the National Reference Laboratory using molecular tests; however, it can take a week or more for results to reach patients and their providers. Since rapid DST is not available at the point of care in Peru, only patients with increased risk of DR-TB receive first-line DST. Yet according to a 2011 study, Peru’s existing recommendations for DST in new TB patients will miss up to three quarters of all new MDR-TB cases, demonstrating the urgent need to adopt rapid DST at the point of TB diagnosis. In another study conducted in Lima in 2003 on community-based therapy for MDR-TB, 75 patients were treated with 58 different regimens, further demonstrating the importance of DST and individualized treatment.

In a recent field visit to Peru, where Treatment Action Group (TAG), an AIDS research and policy think tank fighting for better treatment, a vaccine, and a cure for AIDS, met with TB care providers and programs, providers repeatedly cited the price of rapid molecular diagnostic technologies, specifically GeneXpert and BACTEC MGIT, as a barrier to further decentralization and scale-up of DST. The additional benefits and cost-effectiveness of automated, rapid molecular tests became even clearer after visiting a lab run by the organization Socios en Salud, a sister organization of Partners In Health (PIH) head quartered in Peru. In order to safely conduct DST through culture methods, this lab came equipped with expensive level 3 biosafety outfitting. This level of laboratory capacity and infrastructure remains far from the norm in many of the countries that shoulder the greatest burden of DR-TB.

Beyond insufficient global access to rapid DST is insufficient access to TB drugs–– only 18% of MDR-TB cases worldwide are enrolled in treatment. Pre-approval access to bedaquiline through compassionate use mechanisms saved Dalene’s hearing and life. M/XDR-TB patients with few treatment options living in the many countries without mechanisms for compassionate use have no way to access potentially life-saving experimental drugs. Furthermore, if patients are not able to access new drugs through early access programs pre-approval, as is the case with delamanid, an MDR-TB drug developed by Otsuka, their chances of cure and survival are further diminished. Even worse, many M/XDR-TB patients around the world still struggle to access already approved second-line drugs necessary for their survival, despite their inclusion on the WHO Essential Medicines List.

Given current global progress, only 6 countries can achieve universal access to TB diagnosis and treatment by 2015. With adequate political will and commitment to rapid scale-up of existing tools, many more countries could dramatically improve access to diagnosis and treatment. As Dalene’s husband, Arne, said, “there is life after TB and it can be overcome,” but only if patients have access to timely diagnosis and appropriate treatment. In order to achieve universal access to TB diagnosis and treatment by 2015 and zero TB deaths, new infections, stigma and suffering by 2025, we must first restore urgency to the lethargic and inadequate global response to DR-TB.

♦ ♦ ♦

“Breaking the Record with Dr. Bart Willems,” the third film in the series produced for TAG by director Jonathan Smith, illustrates the story of South African doctor Bart Willems completing treatment for drug-sensitive TB:

Behind the Numbers: Breaking the Record with Dr. Bart Willems from Visual Epidemiology on Vimeo.

Colleen Bio PicColleen Daniels is the TB/HIV project director at Treatment Action Group, an independent AIDS research and policy think tank based in New York.




LM bip picLindsay McKenna is the TB/HIV assistant project officer at Treatment Action Group, an independent AIDS research and policy think tank based in New York.




Twitter: @TAGTeam_Tweets



Lindsay McKenna and Colleen Daniels declare no conflict of interests. The viewpoints expressed here are theirs and do not represent the position of the organizations with which they are affiliated.

  1. Working in one of the country with the highest burden of TB and in a TB diagnostic referral laboratory, this article has opened up my mind and it has left a lot to be desired for. There is a need for politician and many organization to understand the main impact of combatic TB. I’m highly touched and all my life my dream is to make a differences on TB diagnostic and management of TB infection among the patients.

    Thank you very much for this very interesting topic and I encourage people to come out with their idea and examples in order to improve our services and to save more lives and reduce drug toxicity amongst TB patients. New doagnostic tools are quite impressive but we need to build capacity in our regions in order to achieve the Millenium Deveopment Goals by 2015 which is just around the corner.

    I love my job and like reading success stories.

    Many thanks once more!

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