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Cochrane Database of Systematic Reviews

GenoType® MTBDRsl assay for resistance to second-line anti-tuberculosis drugs

Overview of attention for article published in Cochrane database of systematic reviews, September 2016
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  • In the top 25% of all research outputs scored by Altmetric
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Mentioned by

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5 tweeters
facebook
1 Facebook page
wikipedia
1 Wikipedia page

Citations

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52 Dimensions

Readers on

mendeley
175 Mendeley
Title
GenoType® MTBDRsl assay for resistance to second-line anti-tuberculosis drugs
Published in
Cochrane database of systematic reviews, September 2016
DOI 10.1002/14651858.cd010705.pub3
Pubmed ID
Authors

Grant Theron, Jonny Peter, Marty Richardson, Rob Warren, Keertan Dheda, Karen R Steingart

Abstract

Genotype® MTBDRsl (MTBDRsl) is a rapid DNA-based test for detecting specific mutations associated with resistance to fluoroquinolones and second-line injectable drugs (SLIDs) in Mycobacterium tuberculosis complex. MTBDRsl version 2.0 (released in 2015) identifies the mutations detected by version 1.0, as well as additional mutations. The test may be performed on a culture isolate or a patient specimen, which eliminates delays associated with culture. Version 1.0 requires a smear-positive specimen, while version 2.0 may use a smear-positive or -negative specimen. We performed this updated review as part of a World Health Organization process to develop updated guidelines for using MTBDRsl. To assess and compare the diagnostic accuracy of MTBDRsl for: 1. fluoroquinolone resistance, 2. SLID resistance, and 3. extensively drug-resistant tuberculosis, indirectly on a M. tuberculosis isolate grown from culture or directly on a patient specimen. Participants were people with rifampicin-resistant or multidrug-resistant tuberculosis. The role of MTBDRsl would be as the initial test, replacing culture-based drug susceptibility testing (DST), for detecting second-line drug resistance. We searched the following databases without language restrictions up to 21 September 2015: the Cochrane Infectious Diseases Group Specialized Register; MEDLINE; Embase OVID; Science Citation Index Expanded, Conference Proceedings Citation Index-Science, and BIOSIS Previews (all three from Web of Science); LILACS; and SCOPUS; registers for ongoing trials; and ProQuest Dissertations & Theses A&I. We reviewed references from included studies and contacted specialists in the field. We included cross-sectional and case-control studies that determined MTBDRsl accuracy against a defined reference standard (culture-based DST, genetic sequencing, or both). Two review authors independently extracted data and assessed quality using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We synthesized data for versions 1.0 and 2.0 separately. We estimated MTBDRsl sensitivity and specificity for fluoroquinolone resistance, SLID resistance, and extensively drug-resistant tuberculosis when the test was performed indirectly or directly (smear-positive specimen for version 1.0, smear-positive or -negative specimen for version 2.0). We explored the influence on accuracy estimates of individual drugs within a drug class and of different reference standards. We performed most analyses using a bivariate random-effects model with culture-based DST as reference standard. We included 27 studies. Twenty-six studies evaluated version 1.0, and one study version 2.0. Of 26 studies stating specimen country origin, 15 studies (58%) evaluated patients from low- or middle-income countries. Overall, we considered the studies to be of high methodological quality. However, only three studies (11%) had low risk of bias for the reference standard; these studies used World Health Organization (WHO)-recommended critical concentrations for all drugs in the culture-based DST reference standard. MTBDRsl version 1.0 Fluoroquinolone resistance: indirect testing, MTBDRsl pooled sensitivity and specificity (95% confidence interval (CI)) were 85.6% (79.2% to 90.4%) and 98.5% (95.7% to 99.5%), (19 studies, 2223 participants); direct testing (smear-positive specimen), pooled sensitivity and specificity were 86.2% (74.6% to 93.0%) and 98.6% (96.9% to 99.4%), (nine studies, 1771 participants, moderate quality evidence). SLID resistance: indirect testing, MTBDRsl pooled sensitivity and specificity were 76.5% (63.3% to 86.0%) and 99.1% (97.3% to 99.7%), (16 studies, 1921 participants); direct testing (smear-positive specimen), pooled sensitivity and specificity were 87.0% (38.1% to 98.6%) and 99.5% (93.6% to 100.0%), (eight studies, 1639 participants, low quality evidence). Extensively drug-resistant tuberculosis: indirect testing, MTBDRsl pooled sensitivity and specificity were 70.9% (42.9% to 88.8%) and 98.8% (96.1% to 99.6%), (eight studies, 880 participants); direct testing (smear-positive specimen), pooled sensitivity and specificity were 69.4% (38.8% to 89.0%) and 99.4% (95.0% to 99.3%), (six studies, 1420 participants, low quality evidence).Similar to the original Cochrane review, we found no evidence of a significant difference in MTBDRsl version 1.0 accuracy between indirect and direct testing for fluoroquinolone resistance, SLID resistance, and extensively drug-resistant tuberculosis. MTBDRsl version 2.0 Fluoroquinolone resistance: direct testing, MTBDRsl sensitivity and specificity were 97% (83% to 100%) and 98% (93% to 100%), smear-positive specimen; 80% (28% to 99%) and 100% (40% to 100%), smear-negative specimen. SLID resistance: direct testing, MTBDRsl sensitivity and specificity were 89% (72% to 98%) and 90% (84% to 95%), smear-positive specimen; 80% (28% to 99%) and 100% (40% to 100%), smear-negative specimen. Extensively drug-resistant tuberculosis: direct testing, MTBDRsl sensitivity and specificity were 79% (49% to 95%) and 97% (93% to 99%), smear-positive specimen; 50% (1% to 99%) and 100% (59% to 100%), smear-negative specimen.We had insufficient data to estimate summary sensitivity and specificity of version 2.0 (smear-positive and -negative specimens) or to compare accuracy of the two versions.A limitation was that most included studies did not consistently use the World Health Organization (WHO)-recommended concentrations for drugs in the culture-based DST reference standard. In people with rifampicin-resistant or multidrug-resistant tuberculosis, MTBDRsl performed on a culture isolate or smear-positive specimen may be useful in detecting second-line drug resistance. MTBDRsl (smear-positive specimen) correctly classified around six in seven people as having fluoroquinolone or SLID resistance, although the sensitivity estimates for SLID resistance varied. The test rarely gave a positive result for people without drug resistance. However, when second-line drug resistance is not detected (MTBDRsl result is negative), conventional DST can still be used to evaluate patients for resistance to the fluoroquinolones or SLIDs.We recommend that future work evaluate MTBDRsl version 2.0, in particular on smear-negative specimens and in different settings to account for different resistance-causing mutations that may vary by strain. Researchers should also consider incorporating WHO-recommended critical concentrations into their culture-based reference standards.

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Mendeley readers

The data shown below were compiled from readership statistics for 175 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 <1%
Unknown 174 99%

Demographic breakdown

Readers by professional status Count As %
Student > Master 35 20%
Researcher 22 13%
Student > Ph. D. Student 18 10%
Student > Bachelor 13 7%
Student > Doctoral Student 12 7%
Other 29 17%
Unknown 46 26%
Readers by discipline Count As %
Medicine and Dentistry 52 30%
Nursing and Health Professions 10 6%
Biochemistry, Genetics and Molecular Biology 10 6%
Agricultural and Biological Sciences 9 5%
Social Sciences 6 3%
Other 28 16%
Unknown 60 34%

Attention Score in Context

This research output has an Altmetric Attention Score of 6. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 04 June 2020.
All research outputs
#5,102,188
of 20,954,095 outputs
Outputs from Cochrane database of systematic reviews
#7,140
of 12,059 outputs
Outputs of similar age
#75,343
of 286,388 outputs
Outputs of similar age from Cochrane database of systematic reviews
#111
of 176 outputs
Altmetric has tracked 20,954,095 research outputs across all sources so far. Compared to these this one has done well and is in the 75th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 12,059 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 28.5. This one is in the 40th percentile – i.e., 40% of its peers scored the same or lower than it.
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We're also able to compare this research output to 176 others from the same source and published within six weeks on either side of this one. This one is in the 37th percentile – i.e., 37% of its contemporaries scored the same or lower than it.