Background New diagnostic tools are urgently needed to interruptthe transmission of tuberculosis and multidrug-resistant tuberculosis.Rapid, sensitive detection of tuberculosis and multidrug-resistanttuberculosis in sputum has been demonstrated in proof-of-principlestudies of the microscopic-observation drug-susceptibility (MODS)assay, in which broth cultures are examined microscopicallyto detect characteristic growth.
Methods In an operational setting in Peru, we investigated theperformance of the MODS assay for culture and drug-susceptibilitytesting in three target groups: unselected patients with suspectedtuberculosis, prescreened patients at high risk for tuberculosisor multidrug-resistant tuberculosis, and unselected hospitalizedpatients infected with the human immunodeficiency virus. Wecompared the MODS assay head-to-head with two reference methods:automated mycobacterial culture and culture on LöwensteinJensenmedium with the proportion method.
Results Of 3760 sputum samples, 401 (10.7%) yielded culturespositive for Mycobacterium tuberculosis. Sensitivity of detectionwas 97.8% for MODS culture, 89.0% for automated mycobacterialculture, and 84.0% for LöwensteinJensen culture(P<0.001); the median time to culture positivity was 7 days,13 days, and 26 days, respectively (P<0.001), and the mediantime to the results of susceptibility tests was 7 days, 22 days,and 68 days, respectively. The incremental benefit of a secondMODS culture was minimal, particularly in patients at high riskfor tuberculosis or multidrug-resistant tuberculosis. Agreementbetween MODS and the reference standard for susceptibility was100% for rifampin, 97% for isoniazid, 99% for rifampin and isoniazid(combined results for multidrug resistance), 95% for ethambutol,and 92% for streptomycin (kappa values, 1.0, 0.89, 0.93, 0.71,and 0.72, respectively).
Conclusions A single MODS culture of a sputum sample offersmore rapid and sensitive detection of tuberculosis and multidrug-resistanttuberculosis than the existing gold-standard methods used.
Source Information
From the Department of Infectious Diseases and Immunity and the Wellcome Centre for Clinical Tropical Medicine, Imperial College London, Faculty of Medicine (Hammersmith Campus), London (D.A.J.M., C.A.W.E., A.R.E., J.S.F.); Asociación Benéfica PRISMA, San Miguel (D.A.J.M., C.A.W.E., R.H.G., M.-G.H.-D., A.R.E.), Laboratorio de Investigación de Enfermedades Infecciosas, Universidad Peruana Cayetano Heredia, San Martín de Porras (D.A.J.M., C.A.W.E., R.H.G., L.C., J.C., A.R.E.), Hospital Nacional General Arzobispo Loayza (A.V., Y.P.), Hospital Nacional Hipolito Unanue, El Agustino (E.S.), Dirección de SaludIII Lima Norte (Ministerio de Salud), Rimac (J.C.S.), and Dirección de SaludIV Lima Este (Ministerio de Salud), El Agustino (C.S., D.L.) all in Lima, Peru; the Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore (D.A.J.M., C.A.W.E., R.H.G.); and the Tulane School of Public Health and Tropical Medicine, New Orleans (R.O.).
Address reprint requests to Dr. Moore at the Department of Infectious Diseases and Immunity and Wellcome Centre for Clinical Tropical Medicine, Imperial College London, Faculty of Medicine (Hammersmith Campus), DuCane Rd., London W12 0NN, United Kingdom, or at davidajmoore{at}msn.com.
MODS Assay for the Diagnosis of TB
Palomino J.-C., Martin A., Portaels F., Hasan R., Irfan S., Moore D. A.J., Gilman R. H., Friedland J. S.
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N Engl J Med 2007;
356:188-189, Jan 11, 2007.
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