SeriesScale-up of services and research priorities for diagnosis, management, and control of tuberculosis: a call to action
Introduction
Substantial progress has been made in the past 15 years to scale up diagnostic services and treatment of tuberculosis. By 2008, virtually all countries had adopted WHO's Stop TB Strategy; the global case detection rate of sputum-smear-positive tuberculosis rose from 15% in 1995 to 61%, and the treatment success rate from 77% to 87%.1 The establishment of a universal control network for tuberculosis through the Stop TB Partnership, formulation of international standards for case management, use of uniform reporting systems, and regular analysis of reported data to monitor the performance of national tuberculosis control programmes, and also progress toward global control targets, are major achievements. Provision of effective treatment to patients with tuberculosis in even the poorest and most remote parts of the world reduced disease-related suffering and death. Global implementation of the Stop TB Strategy (including directly observed therapy, short course [DOTS]) between 1995 and 2008, was estimated to have cured 36 million people and averted about 6 million deaths, compared with practices in use until 1995. These estimates provide strong motivation for continued and intensified investment in available approaches.
However, despite these important achievements, control of the global tuberculosis epidemic remains elusive, and present control efforts need to be improved if elimination is ever to be achieved. Global burdens of tuberculosis remain unprecedentedly high, especially in countries with concomitant HIV/AIDS or drug-resistant tuberculosis epidemics.2 Reported data indicate huge gaps in the performance of national tuberculosis control programmes—eg, during 2008, an estimated 3·7 million cases of tuberculosis, including 1·6 million with sputum-smear-positive disease (39% of incident cases) were not reported (and many were probably not detected) by DOTS-based programmes; of an estimated 440 000 cases of multidrug-resistant (MDR) tuberculosis, only 30 000 (7%) were diagnosed and few of these had access to optimum treatment; and of the estimated 1·37 million people co-infected with HIV and Mycobacterium tuberculosis, only 100 000 (7·3%) received antiretroviral treatment.1 Another reality is that despite greatly improved funding, many countries (including ten of 22 high-burden countries) remain subject to intermittent drug stockouts even when, because of substantially improved resources, drug supply should be guaranteed in all settings.3 The table shows a summary of limitations associated with different components of the Stop TB Strategy.
In 1982, on the centenary of the discovery of M tuberculosis, the global tuberculosis situation was reviewed in three reports.4, 5, 6 The epidemic was well controlled and transmission rates were rapidly declining in most developed countries, but not in the developing world.4 The author called for standardised regimens of quality-assured drugs and other components of the yet-to-be defined DOTS strategy. Another author speculated that routine radiological screening might have made a substantial but unacknowledged contribution to epidemic control in developed countries.5 An appreciation that continued transmission sustains the epidemic re-emphasises the need for creative strategies to improve early case detection. Others concluded that control of tuberculosis requires well functioning systems, which ultimately depend on people.6 When insufficient effort is made to develop the capacity of people on whom the systems depend, forceful application of policy can easily degenerate into unquestioning dogma, as suggested by the initial exclusive focus on sputum-smear microscopy to diagnose tuberculosis. Since novel interventions will be delivered through existing health-care systems, development of the necessary management skills, with training and retraining of health personnel, are essential. In the absence of an effective vaccine, the irreducible core of any tuberculosis control strategy remains the early identification and successful treatment of individual patients, which requires dedicated health-system strengthening.
Section snippets
Targets for global tuberculosis control
Performance targets for global control of tuberculosis were first formulated during the 44th World Health Assembly in 1991 (panel 1), aiming for a case detection ratio of at least 70% and a treatment cure rate of 85% by 2000.7 The underlying rationale was based on epidemiological estimates that the prevalence, and later the incidence, of tuberculosis would decrease by 5–10% per year if these performance targets were met.8, 9 In the early 1990s, global tuberculosis control efforts in many
Diagnosis, management, and prevention
Efforts to control tuberculosis are at a crossroads and they need to show a convincing effect. Difficulties for patients in accessing adequate care, weak laboratory infrastructure, and poor recording practices need to be acknowledged, and pragmatic new approaches need to be adopted to resolve these issues. Although not substantiated in a randomised trial, same-day on-site microscopy reduces diagnostic delay and helps the early initiation of treatment.17 The use of fluorescence microscopy, with
Paediatric challenge
Although there is increasing appreciation that children make up a substantial proportion of the global tuberculosis burden, childhood tuberculosis remains neglected in many settings in which the treatment of patients with sputum-smear-positive disease is prioritised.33 Despite being preventable and treatable, autopsy evidence suggests that tuberculosis contributes substantially to morbidity and mortality in children younger than 5 years in settings with poor epidemic control.34 Childhood
Tuberculosis and HIV/AIDS
Tuberculosis is the most common opportunistic infection and cause of death among HIV-infected individuals.43 To reduce this risk, strategies to prevent tuberculosis require urgent scale-up. Available strategies include much earlier diagnosis of HIV/AIDS and earlier start of antiretroviral treatment with intensified case finding, isoniazid preventive treatment, and improved infection control, branded by WHO as the 3Is strategy.44, 45 Their mechanisms of action are complementary, either reducing
Research priorities
Tuberculosis remains a major global health threat despite the availability of inexpensive and effective treatment for more than 50 years, indicating the complex interaction of factors that sustain the global epidemic. The pace at which scientific understanding of these factors progresses is greatly hindered by a lack of sufficient funding dedicated to research priorities that have been defined ad nauseam.58, 59, 60, 61, 62, 63, 64, 65 Panel 2 summarises the basic science research priorities
Funds and funding mechanisms
Tuberculosis control, although better funded than in the past, requires far greater resources if we are serious about turning the tide against the global epidemic. However, such resources must be linked to an honest assessment of where current strategies underperform.74 The conventional DOTS strategy achieved notable success in saving lives but proved insufficient in settings where HIV increases susceptibility to tuberculosis or where transmission of drug-resistant tuberculosis is frequent,
Establishment of The Lancet TB Observatory
There is a great need to follow up this call to action (panel 4) and ensure that the pronouncements, requests, and pledges made in this Series on the basis of the best evidence available will promote urgent policy changes. To foster this global need, The Lancet, in collaboration with the Stop TB Partnership, WHO, the Global Fund, and the leading experts participating in this Series, is launching a new initiative The Lancet TB Observatory, which will assess and monitor progress in control of and
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These authors contributed equally.