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      The clinical value of new diagnostic tools for tuberculosis

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      F1000 Medicine Reports
      Medicine Reports Ltd

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          Abstract

          Barriers to global tuberculosis (TB) control include multidrug resistance, HIV infection, and weak health systems. Case detection is critical to TB control and is affected by all three of these. Currently, most low- and middle-income countries (LMICs) rely on direct sputum smear microscopy for diagnosis. Modern culture methods and molecular tests, previously considered too complex or too expensive for implementation in LMICs, are now being introduced there in parallel with a global effort to strengthen laboratories. It remains to be seen whether services based on these tools can be made widely accessible to patients. New point-of-care tests for TB are urgently needed but cannot be expected in the near future. In the meantime, diagnostic tools based on optimized smear microscopy, although less sensitive than reference laboratory tests, may be more accessible and have more impact on case finding. It is a matter of urgency that these improved microscopy services be integrated with services based on rapid methods that can identify multidrug-resistant cases.

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          Most cited references15

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          Reducing the global burden of tuberculosis: the contribution of improved diagnostics.

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            Facing the crisis: improving the diagnosis of tuberculosis in the HIV era.

            Although the human immunodeficiency virus (HIV) infection pandemic has had a catastrophic impact on tuberculosis (TB) control efforts, especially in sub-Saharan Africa, most of the fundamental concepts reflected in the directly observed treatment, short course (DOTS) strategy still hold true in the HIV era. What has changed, and dramatically, is the importance of speedy and accurate TB diagnosis and the difficulty of achieving this. The disproportionate amount of smear-negative disease in sub-Saharan Africa, which shoulders two-thirds of the global burden of HIV infection and acquired immunodeficiency syndrome, has greatly complicated TB case detection and disease control. Now, 15 years after TB rates began to soar in countries where HIV infection is prevalent, we have learned that the conventional approach -- passively waiting for patients with advanced symptomatic disease to make their way to microscopy centers for diagnosis -- has disastrous consequences. Without better diagnostic tools for TB and effective strategies for their implementation, transmission will not be interrupted, mortality will not be checked, and TB will not be controlled in areas where HIV infection is prevalent. Fortunately, a number of technical opportunities exist for the creation of improved diagnostic tests. Developing and exploiting such tests to support TB control in HIV-infected populations is an urgent priority. A substantial public sector effort is under way to work in partnership with the biotechnology industry to accelerate progress toward that goal. In this article, we will define the need for better TB tests and describe technologies being developed to meet that need.
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              A review of the diagnosis and treatment of smear-negative pulmonary tuberculosis.

              Recommendations on the management of smear-negative pulmonary tuberculosis (TB) are still based on the behaviour of this disease in populations unaffected by the human immunodeficiency virus (HIV). Studies prior to the HIV epidemic estimated that there were 1.22 cases of smear-negative and extra-pulmonary TB for each smear-positive case. Patients with smear-negative pulmonary TB were found to be less infectious and to have a lower mortality, but a significant proportion (50%-71%) progressed to active disease justifying treatment. Moreover, a wide variety of regimens also proved effective in the treatment of smear-negative disease in HIV-negative patients. The advent of HIV has changed many of these parameters. Countries affected by both HIV and TB have experienced a disproportionate increase in smear-negative disease. While apparently remaining less infectious than smear-positive cases, HIV-positive patients with smear-negative pulmonary TB are generally more immunocompromised, have more adverse drug reactions, and suffer higher mortality rates on treatment. Clinical decision-making has also been complicated because HIV co-infection broadens the differential diagnoses of smear-negative pulmonary TB to include diseases such as Pneumocystis carinii pneumonia (PCP), pulmonary Kaposi's sarcoma, and Gram-negative bacteraemia. Our approach to smear-negative pulmonary TB must therefore adapt to these changed parameters. Management algorithms based on several features (clinical symptoms, response to antibiotic trials, smear investigations, and chest radiography) have been developed to improve case detection. These algorithms must be validated in each locale because their performance will vary depending on numerous local factors such as the regional prevalence of PCP. Alternative methods of specimen collection, such as sputum induction, and processing must be evaluated. National tuberculosis programmes should also consider extending the use of rifampicin-based short-course chemotherapy (SCC) to new patients with smear-negative disease. This latter intervention, and the much-needed establishment of additional microscopy and culture facilities, will depend on increased financial and technical support from the international community.
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                Author and article information

                Contributors
                Journal
                F1000 Med Rep
                F1000 Medicine Reports
                Medicine Reports Ltd
                1757-5931
                29 April 2009
                2009
                : 1
                : 36
                Affiliations
                [1 ]simpleUNICEF/United Nations Development Programme/World Bank/World Health Organization Special Programme for Research and Training in Tropical Diseases, World Health Organization 20 Avenue Appia, 1211 Geneva 27Switzerland
                [2 ]simpleInternational Union Against Tuberculosis and Lung Disease 68 Boulevard Saint-Michel, 75006 ParisFrance
                [3 ]simpleLondon School of Hygiene and Tropical Medicine Keppel Street, London WC1E 7HTUK
                Article
                36
                10.3410/M1-36
                2924716
                20948745
                3cc1f1aa-15f1-4721-82fa-63deab9866fe
                © 2009 Medicine Reports Ltd

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. You may not use this work for commercial purposes

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