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Validation of a Diagnostic Algorithm for Adult Tuberculous Meningitis

Tuberculous meningitis (TBM) remains difficult to diagnose. We prospectively evaluated a diagnostic algorithm for TBM in 205 HIV-negative patients with meningitis and a low CSF glucose. Patients were classified as having TBM or bacterial meningitis (BM) by two diagnostic methods: logistic regression method (LRM) and classification and regression tree (CART). We performed analyses of TBM versus BM and TBM versus non-TBM in all patients and in patients with microbiologically confirmed diagnoses. Diagnostic sensitivities for TBM were 99% (LRM) and 87% (CART). For BM, diagnostic sensitivities were 81.5% (LRM) and 86.5% (CART) in the primary analysis and 86.5% (LRM) and 74% (CART) in the secondary analysis. In microbiologically confirmed cases, similar rates were achieved. These figures are superior to microbiological confirmation rates in routine laboratories and support the use of this algorithm in high-prevalence TB settings with limited diagnostic facilities. Validation in an HIV-endemic setting is required.

Received October 12, 2006. Accepted for publication May 16, 2007.

Acknowledgments: We thank the doctors and nurses of the Clinical Research Unit and the staff of the Microbiology Department at the Hospital for Tropical Diseases, Ho Chi Minh City.

Financial support: The study was funded by the Wellcome Trust of Great Britain. M.E.T. is a Wellcome Trust Research Training Fellow, G.E.T. is a Wellcome Trust Career Development Fellow, and J.J.F. is a Wellcome Trust Senior Fellow.

^* Address correspondence to M. Estee Török, Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam. E-mail: etorok{at}oucru.org

Contributors: The study was designed by M.E.T., G.E.T., and J.J.F. Data were collected by H.D.T.N., T.T.H.C., and N.T.H.M., and analyzed by M.E.T. and K.S. M.E.T., G.E.T., K.S., and J.J.F. wrote the paper. The final manuscript was reviewed and approved by all authors.

Authors’ addresses: M. Estee Török and Jeremy J. Farrar, Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam, Telephone: +84 8 923 7954, +84 8 923 9211, Fax: +84 8 923 8904, and University of Oxford, Centre for Clinical Vaccinology and Tropical Medicine, United Kingdom, E-mail: etorok{at}oucru.org. Ho Dang Trung Nghia, Tran Thi Hong Chau, and Nguyen Thi Hoang Mai, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam. Guy E. Thwaites, Centre for Medical Microbiology and Infection, Imperial College, London, United Kingdom. Kasia Stepniewska, Wellcome Mahidol Oxford Tropical Medicine Research Programme, Bangkok, Thailand and University of Oxford, Centre for Clinical Vaccinology and Tropical Medicine, United Kingdom.

Reprint requests: M. Estee Török, Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam, Telephone: +84 8 923 7954, +84 8 923 9211, Fax: +84 8 923 8904, E-mail: etorok{at}oucru.org.