Though the global incidence rate of tuberculosis is falling, thanks to wide-scale coordination of standardized anti-TB interventions, the goal of eliminating TB by 2050 will not be met without new technologies and approaches, say specialists at the World Health Organization.

The reasons for the slower-than-hoped-for reduction rate of TB incidence, which now holds at less than 1% per year, are economic, geographic, and technological.

Current diagnostic methods in wide use only detect about 60% of TB cases. Vulnerable people in many poor countries still do not have access to affordable treatment or early diagnosis. Meanwhile multidrug-resistant (MDR) TB remains a threat in some regions, particularly Europe; and HIV infection fuels tuberculosis incidence in other regions, particularly Africa. In 2008 there were an estimated 139 incident cases of TB per 100,000 population, or 11 million worldwide, with 1.8 million associated deaths.

In the first of a series of eight articles on TB interventions, published online ahead of print May 18 in the Lancet, Dr. Knut Lönnroth and Dr. Mario Raviglione of WHO’s Stop TB program in Geneva, along with colleagues in the United States, Kenya, and India, undertook a broad review of published studies and of epidemiologic data to measure progress on TB reduction goals set by WHO and the United Nations between 1990 and 2000 [DOI]. They also surveyed control policies and health systems in 22 nations that together comprise 80% of the world’s TB burden, while noting that data reporting in many of the high-burden countries could be subpar or inconsistent.

The WHO and UN goals included halting and beginning to reverse by 2015 the incidence of TB; halving by 2015 the incidence and death rates of 1990; and reducing TB incidence to one case per million people by 2050. The first goal, Dr. Lönnroth and Dr. Raviglione concluded, may have been met as early as 2004. The second will likely be met in most regions, they said, but not all.

And the third goal, they said, may be out of reach without a reconsideration of overall strategy and further technological improvements.

Though some newer technologies, such as have preventative therapy with isoniazid, are helping and should be expanded, Dr. Lönnroth said in an interview May 18, “we can still wish for a better technology in terms of drug treatment for people with active disease. We want better, simpler diagnostic tools that can be used in peripheral settings, such as rural clinics – a blood test or a dib [antigen] test that can answer the question: ‘Do I have TB?’. And the ultimate thing we can wish for is a new and better vaccine.”

But Dr. Lönnroth noted that there are countless factors affecting TB rates, not all of which can be addressed with technology. “One thing is not going to help the situation,” he said. “It has to be a combination of different types of efforts.”

Combining different types of efforts is also the basic philosophy of directly observed therapy, short course (DOTS), WHO’s standardized package of tuberculosis interventions, which was started in 1995. The key components DOTS include diagnosis through bacteriology, standardized and supervised treatment, an effective drug supply system, and monitoring and evaluation of performance.

Between 1995 and 2008, a period during which DOTS was implemented in 181 countries (including all 22 of the high-burden countries), 36 million people were cured of TB, with an estimated 6 million more lives saved than had DOTS not been adopted, Dr. Lönnroth and Dr. Raviglione wrote. TB fatality rates worldwide dropped by half in that period, from 8% to 4%.

However, case detection rates, after a period of acceleration, leveled off in 2007 at around 60% globally, short of WHO’s goal of 70%. Treatment success under DOTS has proven uneven, with Mediterranean, Pacific, and Southeast Asian countries reporting successful treatment rates as high as 92% in 2007, while Europe and Africa saw 67% and 79% that year, respectively.

Dr. Lönnroth and Dr. Raviglione estimated, using modeling from multiple studies, that detection of incident cases above 70% and treatment rates over 85% would be necessary to produce reductions in the TB rate of 5%-10% per year. Currently, the annual global decline is estimated at a modest .07%.

While the European region, notably Russia, continues to struggle with MDR tuberculosis, inadequate treatment success, and high dropout rates from treatment, it is likely the African situation that will cause the 2015 target of halving the 1990 rates to be missed, Dr. Lönnroth and Dr. Raviglione wrote.

HIV infection increases vulnerability to co-infection with TB by a factor of 20, and the rapid increase in TB incidence and deaths in Africa during the 1990s related to the high regional incidence of HIV, which has only recently begun to decline.

Moreover, reporting and detection remains poor, with less than a quarter of the approximately 1.4 million HIV and TB co-infected people identified in 2008.

In concluding their analysis, the authors made note of the relationship between poverty and the epidemiology of TB, a relationship underscored in an associated editorial by Dr. Richard Horton, the Lancet’s editor in chief, and Dr. Pamela Das, its executive editor. Treatment-related actions alone, Dr. Horton and Dr. Das wrote, “will be insufficient to reach global goals. There is an urgent need to assess interventions for social and economic determinants, such as malnutrition, alcohol use, poor housing, indoor air pollution, and poverty.”

Other papers and related comments in the Lancet series addressed topics including the interaction of age and immunity with TB, the need to strengthen health systems, and the increase services and research priorities for diagnosis, management, and control of tuberculosis.

In a paper on TB vaccines, researchers led by Prof. Stefan H. E. Kaufmann, of Max Planck Institute for Infection Biology in Berlin, said that “after decades of inactivity” in researcher and development for tuberculosis vaccines, 11 candidates are currently in the clinical trial stage. Most of the candidates are intended to replace or be boosters for the recombinant live vaccines (BCG) that is currently in use. The BCG vaccination provides insufficient protection against adolescent and adult TB, and while it is more effective in infants, it has safety issues in those who also have HIV, researchers explained.

The potential for improvement is great, they wrote. A key message of their report is that “New vaccines can contribute to the ambitious goal of reducing the yearly incidence of tuberculosis to less than one new case per million population by 2050,” the authors wrote. However, the efforts are severely underfunded. Costs are projected to be U.S.$2 billion per year price tag over the next 10 years. Some U.S.$400-$500 million was available in 2007-2008.

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