Evaluation of the microscopic observational drug susceptibility assay for rapid and efficient diagnosis of multi-drug resistant tuberculosis

Objectives In Mali early detection and treatment of multidrug resistance tuberculosis (MDR-TB) are still challenging due to cost, time and/or complexity associated with regular tests. Microscopic Observation Drug Susceptibility (MODS) is a low-cost assay validated by WHO in 2010. It is a liquid culture based assay to detect the “cording” characteristic of Mycobacterium tuberculosis complex (MTBc) and to assess susceptibility to both isoniazid and rifampicin defining MDR-TB. In this study we aimed to evaluate the performance of MODS as diagnostic tool compared to a validated method, the MGIT/AST/SIRE. Methods and Results Between January 2010 and October 2015, we included 98 suspected TB patients in an observational cohort study. The sensitivity and specificity of MODS assay for detecting TB were respectively 94.12% and 85.71% compared to the reference MGIT/7H11 culture, with a Cohen Kappa coefficient of 0.78 [95% CI: 0.517-1.043]. The median time to culture positivity for MODS assay and MGIT (plus interquartile range, IQR) was respectively eight days [IQR, 5-11] and six days [IQR, 5-6]. In detecting MDR-TB patients, the sensitivity and specificity of MODS assay were respectively 100% and 95.92%. The positive predictive value and negative predictive values were respectively 66.7% and 100%. The median turnaround time for obtaining MDR-TB results using MODS assay and MGIT/AST/SIRE was respectively nine days and 35 days. Thus, the MODS assay rapidly identifies MDR-TB in Mali than the MGIT/AST/SIRE. Conclusion As an easy, simple, fast and affordable method, the MODS assay could significantly improve the management of tuberculosis.

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“…Our sensitivity of 100% and a specificity of 95.92% for MODS to detect MDR-TB are consistent with other reports (12,21–24). …”

Section: Discussionsupporting

confidence: 92%

“…in 2012 (21), who found a sensitivity of 94.12% and a specificity of 89.39% for MODS and to Zikum et al . in 2015 in China (22) whose also reported a sensitivity between 87.78% and 94.4% and a specificity between 96.8% and 100%, our data showed a good correlation between the MODS assay and a reference tuberculosis test.…”

Section: Discussionmentioning

confidence: 92%

Performance of microscopic observation drug susceptibility for the rapid diagnosis of tuberculosis and detection of drug resistance in Bamako, Mali

Sanogo

Kone

Diarra

et al. 2017

Clinical Microbiology and Infection

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“…However, labor costs are specific to the setting of the study, and the large variability of labor costs will impact the conclusions of cost effectiveness in different settings. Additionally, several studies have shown that the cost for micro broth culture is lower than those of other available culture methods [9], [10], [11] [16]. In the liquid broth assay, 3 positive cultures (1.5%) and 4 negative cultures (3.3%) were contaminated.…”

Section: Discussionmentioning

confidence: 99%

“…Global efforts for TB control, especially in resource limited settings, are being challenged by the lack of rapid, reliable and inexpensive techniques for the detection of M. tuberculosis [7], [8], [9], [10]. Results from the conventional culture detection methods come too late to influence a timely decision on patient management.…”

Section: Introductionmentioning

confidence: 99%

Early and Efficient Detection of Mycobacterium tuberculosis in Sputum by Microscopic Observation of Broth Cultures

et al. 2013

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Early, efficient and inexpensive methods for the detection of pulmonary tuberculosis are urgently needed for effective patient management as well as to interrupt transmission. These methods to detect M. tuberculosis in a timely and affordable way are not yet widely available in resource-limited settings. In a developing-country setting, we prospectively evaluated two methods for culturing and detecting M. tuberculosis in sputum. Sputum samples were cultured in liquid assay (micro broth culture) in microplate wells and growth was detected by microscopic observation, or in Löwenstein–Jensen (LJ) solid media where growth was detected by visual inspection for colonies. Sputum samples were collected from 321 tuberculosis (TB) suspects attending Bugando Medical Centre, in Mwanza, Tanzania, and were cultured in parallel. Pulmonary tuberculosis cases were diagnosed using the American Thoracic Society diagnostic standards. There were a total of 200 (62.3%) pulmonary tuberculosis cases. Liquid assay with microscopic detection detected a significantly higher proportion of cases than LJ solid culture: 89.0% (95% confidence interval [CI], 84.7% to 93.3%) versus 77.0% (95% CI, 71.2% to 82.8%) (p = 0.0007). The median turn around time to diagnose tuberculosis was significantly shorter for micro broth culture than for the LJ solid culture, 9 days (interquartile range [IQR] 7–13), versus 21 days (IQR 14–28) (p<0.0001). The cost for micro broth culture (labor inclusive) in our study was US $4.56 per sample, versus US $11.35 per sample for the LJ solid culture. The liquid assay (micro broth culture) is an early, feasible, and inexpensive method for detection of pulmonary tuberculosis in resource limited settings.

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“…Due to its high cost, Middlebrook media are rarely used routinely in countries with limited resources. Thin layer agar (TLA) is a solid medium-based test, which, on a similar principle as the Microscopic Observation Drug Susceptibility assay (MODS) method (Lazarus et al, 2012 ), relies on the inoculation on a thin layer of Middlebrook 7H11 agar for the detection of cording M. tuberculosis microcolonies using an inverted microscope (Runyon, 1970 ). Later, incidental isolation of M. tuberculosis on blood agar (Drancourt and Raoult, 2007 ) suggested that this routine medium could support isolation of M. tuberculosis .…”

Section: Introductionmentioning

confidence: 99%

Rapid culture-based diagnosis of pulmonary tuberculosis in developed and developing countries

Asmar

Drancourt

2015

Front. Microbiol.

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Culturing Mycobacterium tuberculosis remains the gold standard for the laboratory diagnosis of pulmonary tuberculosis, with 9 million new cases and 1.5 million deaths mainly in developing countries. Reviewing data reported over 20 years yields a state-of-the-art procedure for the routine culture of M. tuberculosis in both developed and developing countries. Useful specimens include sputum, induced sputum, and stools collected in quaternary ammonium preservative-containing sterile cans. The usefulness of other non-invasive specimens remains to be evaluated. Specimens can be collected in a diagnosis kit also containing sampling materials, instructions, laboratory requests, and informed consent. Automated direct LED fluorescence microscopy after auramine staining precedes inoculation of an egg-lecithin-containing culture solid medium under microaerophilic atmosphere, inverted microscope reading or scanning video-imaging detection of colonies and colonies identification by recent molecular methods. This procedure should result in a diagnosis of pulmonary tuberculosis as fast as 5 days. It may be implemented in both developed and developing countries with automated steps replaceable by manual steps depending on local resources.

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Evaluation of the microscopic observational drug susceptibility assay for rapid and efficient diagnosis of multi-drug resistant tuberculosis

Abstract: MODS was found to be a sensitive and rapid alternative method for performing culture and DST to identify MDR-TB in resource poor settings.

Cited by 11 publications

References 4 publications

Performance of microscopic observation drug susceptibility for the rapid diagnosis of tuberculosis and detection of drug resistance in Bamako, Mali

Performance of microscopic observation drug susceptibility for the rapid diagnosis of tuberculosis and detection of drug resistance in Bamako, Mali

Early and Efficient Detection of Mycobacterium tuberculosis in Sputum by Microscopic Observation of Broth Cultures

Rapid culture-based diagnosis of pulmonary tuberculosis in developed and developing countries

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