Facing up to failure on World TB Day

26 Mar 2010

Patrick Adams

Source: TropIKA.net

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Over the past decade, increased funding, political will and advances in medical science have yielded important achievements in global health. Successes include major progress against polio, the eradication of which is now well within reach; the halving of malaria deaths in several of sub-Saharan Africa’s worst-affected countries following the scale-up of insecticide-treated bed nets and indoor residual spraying (IRS); and the development of the first-ever AIDS vaccine which it is claimed will protect a significant minority of humans against the disease.

Every March 24th, however, the world confronts its collective failure to use medical advances to stop the spread of tuberculosis among the poor. Despite the existence of cheap and effective treatment for more than half a century, the airborne disease continues to kill roughly 5,000 people every day and an estimated 1.8 million people every year, making it the second leading cause of adult death by an infectious disease. Just as it did throughout the 18th and 19th centuries, TB thrives in overpopulated, impoverished communities with poor nutrition and limited access to care.

Yet the TB of 2010 is not the TB of 1850 or even 1950. M. tuberculosis has evolved and the situation has drastically changed; now multidrug-resistant (MDR), extensively drug-resistant (XDR) and even extremely drug-resistant (XXDR) strains of the disease circulate the globe, threatening to reverse many of the gains made to date. According to WHO, there were 440,000 MDR-TB cases in 2008, accounting for 3.6% of incident TB cases worldwide, an all-time high. (Data from parts of northwest Russia reveal that a staggering 1 in 4 new TB cases is MDR-TB.) As of March 2010, 58 countries had reported at least one case of XDR-TB, and there are believed to be an estimated 25,000 new cases of the disease every year. And last year, the first reported case of XXDR in the United States made the headlines.

WHO expects 29,000 MDR-TB cases to be treated in 2010, and a major expansion of services is under way. But given that a mere 6 000 patients were reached in 2008, those expectations are not likely to be met – particularly if the resources are not made available. Dr Marcos Espinal, executive secretary of the Stop TB Partnership, has called funding the most serious challenge to current efforts. Between 2006 and 2008, the financing need for funding TB control worldwide was short by $1 billion per year. The budget shortfall for research and development in 2007 was $0.5 billion.

Compounding the crisis is the deadly interaction of tuberculosis with HIV/AIDS. Despite the improved availability of TB drugs through the WHO Global Drugs Facility (GDF), the mechanism for anti-TB chemotherapy and the universal scale-up ARVs, developing countries are faced with a soaring burden of HIV-driven TB. Of the 1.8 million TB deaths in 2008, approximately half a million were associated with HIV – many of them because they were not enrolled on anti-retroviral therapy.

In its 2009 Global Tuberculosis Control Report released on last year’s World TB Day, WHO presented data showing rates of TB-HIV co-infection twice as high as originally estimated. Much progress has been made in the past year; 200,000 more TB patients were tested for HIV; one-third of the patients who tested positive were started on ART and the remaining two-thirds were enrolled on cotrimoxazole prophylaxis to prevent fatal bacterial infections. But there is still much to be done. Those numbers represent less than a third of the target population set for 2009 in the Global Plan to Stop TB (2006-2015).

Key areas of research with respect to TB-HIV co-infection include the need to define the optimal timing of ARV therapy during TB treatment and to address the frequent occurrence of immune reconstitution inflammatory syndrome (IRIS) in TB patients, especially those with advanced HIV-related immune deficiency. Perhaps the most pressing need, however, is to find alternatives to current drug regimens in order to minimize side effects from drug interactions and reduce the long duration of TB treatment. While a number of new drugs are currently being developed and tested in clinical trials, the front-line anti-TB therapy is still rifampicin, as it has been for more than 40 years.

Still, despite the length and rigour of the drug discovery process, new initiatives, like the Critical Path to TB Drug Regimens (featured in a recent TropIKA.net article), offer reason for hope that a new TB drug will arrive soon. The CPTR, a public-private collaboration sponsored by the US Food and Drug Administration (FDA), aims to accelerate the search for new drugs by testing promising combinations of individual TB drug candidates from different companies early in the pipeline.

Equally important is providing access to existing second-line drugs for the hundreds of thousands of patients suffering from strains resistant to the front-line isoniazid-rifampicin combination. Since launching in 2000, the Green Light Committee (GLC) Initiative, a technical advisory body to the Stop TB Partnership and WHO, has helped more than 70 countries and territories procure treatment for approximately 63 000 MDR-TB patients. As of the end of 2009, 19 000 patients with MDR-TB were reported to have been enrolled in 44 GLC sites. Of the estimated cases emerging in 2008, however, only 1% were enrolled in treatment by the GLC projects.

Also worrying is the fact that only a small fraction of people infected with MDR-TB are being diagnosed – an estimated 7% of all cases. According to the Foundation for Innovative New Diagnostics (FIND), TB in general is vastly underdiagnosed, with as many as 1.6 million smear-positive cases unreported in 2008. Rapid, reliable and practical point-of-care diagnostic tools are urgently needed to ensure proper and timely treatment.

A number of promising new tools, such as the Line Probe Assay (LiPA), endorsed by the WHO, represent important advances for the diagnosis and management of drug-resistant TB. However, LiPA is prohibitively expensive for impoverished communities in the developing world. Moreover, in countries with a heavy burden of disease, the infrastructure required to implement new tools is lacking or non-existent, and access to the most current information on new advances is severely limited.

In an effort to fill that gap, the Stop TB Partnership’s New Diagnostics Working Group recently launched the website www.tbevidence.org, a comprehensive resource for TB diagnosis, providing detailed information on evidence syntheses, policies, guidelines and research agendas. The site features systematic reviews on the accuracy of tests, information on available commercial kits, training requirements, news from the diagnostics community and updates on the pipeline of improved tools for TB diagnosis.

Meanwhile, TDR has made it easier for tuberculosis researchers to work more effectively with academics, officials and industry professionals and to identify the most promising TB tests through the publication of Pathways to better diagnostics for tuberculosis, a “blueprint for the development of TB diagnostics.” (See TropIKA.net article.) By offering a structure to guide researchers involved in diagnostic development through the process – “from discovery to delivery” – the authors aim to help align the development of new tools with the needs and requirements of the areas where the burden of TB is greatest.

World TB Day, first recognized in 1982, is intended to strengthen public awareness about the global TB epidemic and current efforts to eliminate the disease. And while on this World TB Day, the international community has much to be concerned about, there is good news to report as well. The global incidence rate of TB is falling, if very slowly. And in 2008, for the first time in a decade, the treatment rate of regular TB exceeded the 85% target. If these trends are to continue, funders, policymakers and public health experts alike must maintain their focus. To eliminate TB as a public health problem, every day must be World TB Day.