Correspondence
MODS Assay for the Diagnosis of TB
N Engl J Med 2007; 356:188-189January 11, 2007
- Article
To the Editor:
In their article on the use of microscopic-observation drug-susceptibility (MODS) culture for the diagnosis and direct detection of multidrug-resistant tuberculosis, Moore et al. (Oct. 12 issue)1 state that MODS culture offers faster and more sensitive results than existing gold-standard methods. This study is one of the few performed in a target population with a rather simple and inexpensive method that seems to be appropriate for countries with limited resources.
However, we would like to stress that there are other options that have recently been described2 and are currently under evaluation. As compared with MODS culture, the nitrate reduction assay, based on a simple procedure involving the use of Löwenstein–Jensen medium, has been tested in sputum samples with similarly good results.3 The thin-layer agar method, which is similar to MODS culture but with solid medium and standard microscopes, had better results than conventional methods when evaluated in target populations.4 In ongoing evaluations, the thin-layer agar method has also outperformed the reference method for detecting multidrug-resistant tuberculosis. In addition, direct colorimetric methods with redox indicators have performed very well5 and are under further evaluation. A disadvantage of the MODS method remains the requirement of an inverted microscope, which is not routinely available in laboratories that perform diagnostic tests for tuberculosis.
5 ReferencesJuan-Carlos Palomino, Ph.D.
Anandi Martin, Ph.D.
Francoise Portaels, Ph.D.
Institute of Tropical Medicine, 2000 Antwerp, Belgium
jcpalomino@itg.be 1
Moore DAJ ,Evans CAW ,Gilman RH , et al. Microscopic-observation drug-susceptibility assay for the diagnosis of TB. N Engl J Med 2006;355:1539-1550
Full Text | Web of Science | Medline2
Palomino JC . Newer diagnostics for tuberculosis and multi-drug resistant tuberculosis. Curr Opin Pulm Med 2006;12:172-178
CrossRef | Web of Science | Medline3
Musa HR ,Ambroggi M ,Souto A ,Angeby KA . Drug susceptibility testing of Mycobacterium tuberculosis by a nitrate reductase assay applied directly on microscopy-positive sputum samples. J Clin Microbiol 2005;43:3159-3161
CrossRef | Web of Science | Medline4
Robledo JA ,Mejia GI ,Morcillo N , et al. Evaluation of a rapid culture method for tuberculosis diagnosis: a Latin American multi-center study. Int J Tuberc Lung Dis 2006;10:613-619
Web of Science | Medline5
Abate G ,Aseffa A ,Selassie A , et al. Direct colorimetric assay for rapid detection of rifampin-resistant Mycobacterium tuberculosis. J Clin Microbiol 2004;42:871-873
CrossRef | Web of Science | Medline
To the Editor:
The MODS assay has certain limitations. Microscopical differentiation between microcolonies of Mycobacterium tuberculosis and those of rapidly growing mycobacteria may be difficult. The assay requires daily examination, is time-consuming, and as highlighted by Iseman and Heifets,1 carries a risk of laboratory transmission. We therefore agree that the microscopical-observation method, although promising, will require modification and adaptation before it can be recommended for widespread use.
1 ReferencesRumina Hasan, M.B., B.S., Ph.D.
Seema Irfan, M.B., B.S.
Aga Khan University, Karachi 74800, Pakistan
rumina.hasan@aku. edu 1
Iseman MD ,Heifets LB . Rapid detection of tuberculosis and drug-resistant tuberculosis. N Engl J Med 2006;355:1606-1608
Full Text | Web of Science | Medline
Author/Editor Response
Although there is merit in the alternative methods Palomino and colleagues mention, elements of which gave rise to the MODS assay, the culture time for the Löwenstein–Jensen–based nitrate reduction assay is three to four times that for the MODS assay, with lower sensitivity, and as with the direct colorimetric assay, data for smear-negative samples are lacking. Unlike MODS culture, both techniques involve the potentially hazardous opening of mature tuberculosis cultures to add a specific reagent. The thin-layer agar method is rapid, but its sensitivity is usually lower and its contamination rate higher than those of the Löwenstein–Jensen method, and no data on drug-susceptibility testing have been published.
In our opinion, MODS culture is actually safer than any indirect drug-susceptibility testing method, since culture amplification and direct drug-susceptibility testing occur within a closed system: the MODS plate is inoculated and then sealed within a ziplock bag. It is not manipulated again, since all readings, including those for drug-susceptibility testing, are done through the bag. The handling of cultured M. tuberculosis at bacterial concentrations thousands of times those of clinical specimens, which is required for secondary drug-susceptibility testing, dwarfs the biohazard risk associated with sputum-decontamination processes common to all culture methods. This handling risk is entirely avoided with the MODS assay.
Hasan and Irfan did not use ziplock bags, because this important detail was omitted from previous articles on the MODS assay.1-3 We do not believe that a MODS laboratory needs to meet biosafety level 3 standards. Combining the use by laboratory staff of respirators approved by the National Institute for Occupational Safety and Health and appropriate protective clothing with a well-positioned, properly maintained class II biologic safety cabinet that recirculates exhausted air through a high-efficiency particulate air (HEPA) filter into a closed room, should be adequate. With respect to rapidly growing mycobacteria, these organisms should overgrow MODS plates by day 5, a phenomenon not seen with M. tuberculosis.
3 ReferencesDavid A.J. Moore, M.D.
Imperial College Wellcome Centre for Clinical Tropical Medicine, London W12 0NN, United Kingdom
davidajmoore@msn.com Robert H. Gilman, M.D.
Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205Jon S. Friedland, M.D., Ph.D.
Imperial College Wellcome Centre for Clinical Tropical Medicine, London W12 0NN, United Kingdom1
Moore DA ,Mendoza D ,Gilman RH , et al. Microscopic observation drug susceptibility assay, a rapid, reliable diagnostic test for multidrug-resistant tuberculosis suitable for use in resource-poor settings. J Clin Microbiol 2004;42:4432-4437
CrossRef | Web of Science | Medline2
Caviedes L ,Lee TS ,Gilman RH , et al. Rapid, efficient detection and drug susceptibility testing of Mycobacterium tuberculosis in sputum by microscopic observation of broth cultures. J Clin Microbiol 2000;38:1203-1208
Web of Science | Medline3
MODS user guide. Lima, Peru: MODS Group of Peru, November 2006. (Accessed December 20, 2006, at http://www.upch.edu.pe/facien/dbmbqf/mods/mods.htm.)
- Citing Articles (1)
Citing Articles
1
Y. Ben Amor, M. Fraden, J. Ruxin. (2008) Reversing the tide of tuberculosis in India: complementing microscopy with line probe assays. Global Public Health 3:4, 399-416
CrossRef
